The Eunice
Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) and Office of Dietary Supplements (ODS), National
Institutes of Health (NIH) encourages innovative, multidisciplinary, interactive,
and synergistic program project (P01) grant applications from
institutes/organizations that propose to integrate basic, translational, and
clinical approaches to understanding the developmental biology and genetic
basis of congenital structural human malformations. To contain costs, each
P01 will consist of only three component projects and associated cores. At
least one project must propose basic research in an animal model system and
at least one project must be clinical or translational in nature. The
component projects must share a common central theme, focus, or objective on
a specific developmental structural malformation or class of anomalies that
is genotypically, mechanistically, biologically, or phenotypically analogous
or homologous in both animal models and humans.

(Now Expired July 25, 2013 per issuance of PAR-13-285), Originally January 8, 2015

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the PHS398
Application Guide except where instructed to do otherwise (in this FOA or
in a Notice from the NIH Guide
for Grants and Contracts). Conformance to all requirements (both in
the Application Guide and the FOA) is required and strictly enforced. While
some links are provided, applicants must read and follow all application
instructions in the Application Guide as well as any program-specific
instructions noted in Section IV. When
the program-specific instructions deviate from those in the Application Guide,
follow the program-specific instructions. Applications that do not
comply with these instructions may be delayed or not accepted for review.

Looking ahead: NIH is committed to transitioning all
grant programs to electronic submission using the SF424 Research and Related
(R&R) format and is currently investigating solutions that will accommodate
NIH’s multi-project programs. NIH will announce plans to transition the
remaining programs in the NIH
Guide to Grants and Contractsand on NIH’s Applying Electronically website.

The Eunice
Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) and Office of Dietary Supplements (ODS), National
Institutes of Health (NIH) encourages innovative, multidisciplinary, interactive,
and synergistic program project (P01) grant applications from
institutes/organizations that propose to integrate basic, translational, and
clinical approaches to understanding the developmental biology and genetic
basis of congenital structural human malformations. To contain costs, each P01
will consist of only three component projects and associated cores. At least
one project must propose basic research in an animal model system and at least
one project must be clinical or translational in nature. The component
projects must share a common central theme, focus, or objective on a specific
developmental structural malformation or class of anomalies that is
genotypically, mechanistically, biologically, or phenotypically analogous or
homologous in both animal models and humans.

Background

Annually, almost five percent of all live births in the
United States (more than 180,000 babies) involve babies born with birth
defects, as broadly defined to include both structural and functional/metabolic
abnormalities. Next to accidents, birth defects are the leading cause of
death in children; they account for half of all pediatric
hospitalizations. In terms of economic costs, billions of dollars are
spent over the lifetimes of children born with any of 17 major, severe,
nonfatal birth defects. In sum, structural birth defects have a great
impact on public health, socioeconomics, and family life. A high priority
goal of NICHD’s strategic plan is to address the problem of structural birth
defects.

The Developmental Biology, Genetics and Teratology Branch at
NICHD has supported a Birth Defects Initiative since 2000 by funding a number
of research grants and program project grants focused on the use of molecular
genetic approaches for the study of the genetic susceptibility, genetic epidemiology,
and developmental biology of human congenital structural malformations.
These grants established the basis for the Birth Defects Working Group whose
investigators meet annually to present research updates, share ideas and technical
advances, establish new collaborations, and provide input and advice to NICHD
staff. The objective is to capitalize on the rapid and revolutionary
discoveries occurring as a result of the Human Genome Project with the ultimate
goal of enhancing the translation of basic knowledge and insights from
functional genomic studies into development of new, innovative, and efficacious
strategies for the molecular diagnosis, treatment, and prevention of human
structural birth defects. Investigators funded through this FOA will
become part of NICHD’s Birth Defects Working Group comprised of investigators
funded through prior FOAs under NICHD’s Birth Defects Initiative.

This FOA encourages P01 applications in order to broaden the
base of basic scientists and clinicians involved in the Birth Defects Working
Group, to enhance this research effort, and to promote the translation of
advances from the bench to bedside.

Scope

This FOA encourages research on developmental defects of
generalized body patterning and localized dysmorphic anomalies across a variety
of organ systems, such as the skeletal, nervous, gut, cardiac, and lymphatic
systems, that lead to clinically significant and major congenital structural
malformations. In particular, studies that focus on modifier genes and
the role of quantitative aspects of development, such as gene dosage or copy
number variation, as well as imaging of developmental processes are encouraged.
While applications that focus on developmental disorders that result in intellectual
disabilities and related neurobehavioral disabilities are of interest to the
NICHD, they are outside the scope of this FOA. However, studies that
address syndromes of which intellectual disabilities are a part of the
phenotype will be considered as long as the project focuses only on the
structural defects associated with the phenotype.

Proposed projects must be innovative, multidisciplinary,
interactive, and synergistic. They must integrate basic, translational,
and clinical approaches to understanding the developmental biology and genetic
basis of congential structural human malformations. To contain costs,
each P01 will consist of only three component projects and associated
cores. At least one project must use basic research in an animal model
system and at least one project must be clinical or translational in nature.
The component projects must share a common central theme, focus, or objective
on a specific developmental structural malformation or class of anomalies that
is genotypically, mechanistically, biologically, or phenotypically analogous or
homologous in both animal models and humans.

The basic science component projects may include but are not
limited to studies to: 1) identify and characterize the genes, gene modifiers,
gene products, mutations, polymorphisms, or multigene and gene/environment
interactions that play a role in normal and abnormal embryonic patterning and
organogenesis; 2) elucidate the developmental biological processes and
pathways, the biochemical, biophysical, cellular, molecular, genetic
mechanisms, or spatial and temporal gene expression patterns which are involved
in dysmorphogenesis; and/or 3) examine how teratogens and nutritional
deficiencies disrupt or modify gene expression and basic developmental
processes.

The translational/clinical component projects may include
but are not limited to studies to: 1) characterize and classify genotypes and
phenotypes of human malformations that are comparable in the animal models
being examined; 2) develop physical, genetic, and comparative maps for genes
involved in human malformations; 3) identify the developmental genetic
processes and molecular pathogenesis of human malformations utilizing animal
models; and 4) develop innovative molecular genetic methods, technologies, and
strategies to enhance the diagnosis of human malformations or aid in the
intervention to ameliorate the formation of the birth defects.

Applicants are encouraged to collaborate with existing
population-based birth defects registries, databases, and surveillance programs
at the private, state, and Federal levels, especially the Centers for Disease
Control and Prevention (CDC) Centers of Excellence for Birth Defects.
Applicants are encouraged to initiate collaborations with the CDC Centers to
avail themselves of these valuable resources.

Applicants are encouraged to apply recent technological
advances in developmental biology and genetics in their projects and to utilize
the many existing research resources, bioinformatic databases, and
biotechnological tools in their research cores. The research cores should be
structured to share work effort and research resources (e.g., biotechnology,
high-throughput instrumentation, microarrays, oligonucleotide chips, animal
model development, and technical assistance) among the research projects. The aim
of a core is to provide support and enhance the progress, productivity,
cost-effectiveness, and outcome of the research projects.

Applications may include, but are not limited to, new and
innovative approaches to investigate: 1) genetic and epigenetic defects,
nutritional deficiencies, and teratogens that perturb, modify, or alter gene
expression during early development; 2) the identity and function of
transcription and growth factors in normal and abnormal gastrulation,
embryogenesis, organogenesis, and patterning, as well as their modification by
environmental agents; and 3) defective embryonic developmental processes and
pathways that ultimately lead to malformations.

Areas of research appropriate for this FOA include, but are
not limited to:

Studies of developmental genes, gene products, transcription
factors, small RNAs, and growth factors that function and interact to regulate
cell proliferation, cell differentiation, apoptosis, cell migration, or cell
fate during normal embryonic development and abnormal development leading to a
structural defect;

Studies to identify, map, and characterize genes that play a role
in signal transduction and biochemical pathways, cell fate determination,
gastrulation, embryogenesis, organogenesis, or body patterning and how
developmental defects, mutations, or susceptible polymorphisms lead to
malformations;

Studies using a systems biology approach toward understanding the
complex networks of interactions between numerous genes and proteins
controlling normal and abnormal development;

Studies to understand how disruptions in biophysical and
biomechanical processes might lead to known structural defects;

Investigations into the use of small molecules to identify those
that ameliorate a structural defect;

Investigations of pharmaceutical, nutritional, and teratogenic
agents and factors that alter genes and developmental processes and pathways
that result in dysmorphologies;

Examination of genes and molecular mechanisms and interactions
that control normal and abnormal body axes and symmetry during development;

Investigations of the role of imprinting and epigenetic factors
in developmental processes and formation of major congenital malformations;

Investigations to characterize and classify genotype/phenotypes
of hereditary human malformations and correlate them to homologs in animal
models;

Development and validation of new and/or improved animal models
to study the genes, mutations, mechanisms, and developmental processes and
pathways that cause human malformations;

Efforts to define pleiotropic effects that genes and their
modifiers have in the spatial and temporal development of embryonic and/or
fetal anomalies;

Imaging and gene expression studies to investigate and monitor
the developmental pathogenesis of dysmorphic features;

Investigation of the influence of gene dosage on developmental
processes and the etiology of birth defects;

Examination of the role and developmental biology of neural crest
cells and how defects in their cell proliferation, differentiation, migration,
and patterning may result in major structural birth defects;

Identification and characterization of polymorphisms/mutations of
metabolic genes that function in the development of structural birth defects.

The topics listed above are only examples, are not in
priority order, and are not intended to be all-inclusive. Investigators are
encouraged to explore and develop new, innovative projects and research cores
that are consistent with the overall objectives of this FOA.

Research
Cores

The aim of a core is to provide support and enhance the
progress, productivity, cost-effectiveness, and outcome of the research
projects. Applicants are encouraged to make use of recent technological
advances in developmental biology, genetics, and genomics in their projects
and, when applicable, to utilize resources via research cores. The research
cores should be structured to share work effort and research resources (e.g.,
biotechnology, high-throughput instrumentation, microarrays, oligonucleotide
chips, animal model development, and technical assistance) among the research
projects in the most cost-effective manner. A core must be utilized by at
least two of the three component projects, preferrably by all three.

Participation
in NICHD’s Structural Birth Defects Meetings

The PD(s)/PI(s) for the overall grant and the principal
investigators for each component project should plan to attend an NICHD-sponsored
three-day meeting generally held on an annual basis in the Washington, D.C.
metropolitan area. Funds to pay for this travel should be included in the
budget request. The meeting will provide an opportunity for all investigators
funded through NICHD’s Birth Defects Initiative to communicate, discuss the
progress of their research, exchange ideas and information, share resources,
foster collaborations that are relevant to the research goals of the Birth
Defects Initiative, and provide input and advice to NICHD staff. This
requirement is designed to establish an interactive group of investigators who
are interested in multidisciplinary approaches to enhancing our understanding
of the genetic epidemiology, etiology, pathogenesis, developmental biology, and
genetics of structural birth defects.

Section
II. Award Information

Funding Instrument

Grant

Application Types Allowed

New
Renewal
Resubmission
Revision

The OER Glossary and the PHS398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH
appropriations, and the submission of a sufficient number of meritorious
applications.

Award Budget

Funding
caps for P01 grants are as follows:

For new applications, the first-year cap is $750,000
direct costs, with a cumulative cap of $4,000,000 direct costs over a 5-year
period. For renewal applications, the first-year direct cost maximum is
either $750,000 or an amount 10% above the direct costs awarded in the last
non-competing year, whichever is greater. In addition, there is a
cumulative cap of $5,000,000 in direct costs over a 5-year award
period. For the purpose of funding caps, the calculation of total
direct costs may exclude all facilities and administrative (indirect) costs,
including those indirect costs associated with subcontracts.

Because the nature and scope of the proposed research will
vary from application to application, it is anticipated that the size and
duration of each award will also vary. Although the financial plans of the NICHD
provide support for this program, awards pursuant to this funding opportunity
are contingent upon the availability of funds.

Facilities and administrative costs requested by
consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

Award Project Period

A five-year total project period for P01 programs is
encouraged, but is not mandatory. The minimum total project period is three
years. There must be at least three component research projects at all times
during the grant period.

NIH grants policies as
described in the NIH
Grants Policy Statement will apply
to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations
as described in the PHS398 Application Guide to be eligible to apply for or
receive an award. Applicants must have a valid Dun and Bradstreet Universal
Numbering System (DUNS) number in order to begin each of the following
registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.

All registrations must be completed by the application due
date. Applicant organizations are strongly encouraged to start the registration
process at least4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

The Program Director(s)/Principal Investigator(s) (PD(s)/PI(s))
of the overall P01 should be an established scientist with demonstrated
administrative capabilities. Component Research Projects should be led by
experienced scientists (Subproject Directors) with a variety of disciplinary
and specialty backgrounds. The Core units should be led by investigators (Core
Directors) with appropriate scientific and technical expertise. The PD(s)/PI(s)
and component Subproject Directors should be able to collaborate productively
so that new scientific information may be freely exchanged and effectively
applied by others in the program.

For institutions/organizations proposing multiple PD(s)/PI(s),
visit the Multiple Program Director(s)/Principal Investigator(s) Policy and
submission details in the Senior/Key Person Profile (Expanded) Component of the
PHS398 Application Guide. An investigator can have multiple roles, e.g., as a
multiple PD(s)/PI(s) for the overall application and as a Subproject Director.
There can be multiple directors for a subproject, in which case applicants must
submit a leadership plan for the component project. People designated as
Subproject Directors do not lose their New Investigator or Early Stage
Investigator status.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA
that is essentially the same as one currently pending initial peer review
unless the applicant withdraws the pending application. NIH will not accept any
application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission
Applications from the PHS398 Application Guide.

Section
IV. Application and Submission Information

1. Address to Request Application Package

Applicants are required to prepare applications according to
the current PHS 398 application forms in accordance with the PHS 398
Application Guide.

2. Content and
Form of Application Submission

It is critical that applicants follow the instructions in
the PHS398
Application Guide, except where instructed in this funding opportunity
announcement to do otherwise. Conformance to the requirements in the
Application Guide is required and strictly enforced. Applications that are out
of compliance with these instructions may be delayed or not accepted for review.

Application Submission

Applications must be prepared using the PHS 398 research
grant application forms and instructions for preparing a research grant
application. Submit a signed, typewritten original of the application, including
the checklist, and three signed photocopies in one package to:

For Resubmission or Revision applications, also include the following:

Introductions (required for a resubmission or revision
application)

For overall P01 1
page

For each Research Project (subproject) 1 page

For each Core Unit 1
page

Research Grant Table of Contents

In lieu of the preprinted Table of Contents outline on Form
Page 3 of PHS 398, a Table of Contents should be prepared listing all of the
major sections described below and paginated to enable reviewers to find
specific information easily.

SECTION
I: PRELIMINARY PAGES

Face
Page (Form Page 1)

Complete all items on the application's face page. For
Item 2, enter the number of this FOA and the title, "Developmental
Mechanisms of Human Structural Birth Defects (P01)”. Number succeeding
pages consecutively.

Describe briefly the proposed research program, indicate the
research emphasis of the component Research Projects, and identify the purpose
of the proposed Core units.

List all Senior/Key personnel and Other Significant
Contributors engaged on the project. Use continuation pages as necessary,
numbering consecutively.

Table
of Contents (Form Page 3)

Prepare the Table of Contents including the major headings
as noted above.

Budget
Instructions (Form Page 4):

Prepare a series of composite budget tables for the P01
grant as requested below, followed by a detailed budget for each Research
Project component and each Core unit.

Composite
Budget

Use PHS-398 Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET
PERIOD," to present the total budget for all requested support for
the first year. For each category, such as "Personnel,"
"Equipment," etc., give the amount requested for each Research
Project component and each Core unit, with subtotals.

If consortium arrangements involving other institutions or
organizations are anticipated, include total (direct and indirect) costs
associated with such third-party participation in the Consortium/Contractual
Costs category. Costs for purchased services should be itemized under the
"Other Expenses" category.

Use PHS-398 Form Page 5, "BUDGET FOR ENTIRE PROPOSED PROJECT
PERIOD," to prepare a budget, by category, that provides totals for each
year of requested support. Requests for any increases in succeeding years must
be justified in the individual Research Project component and Core unit
budgets.

Budgets
for Individual Research Project Component and Core Component

Detailed Budget for Initial Budget Period (use PHS-398 Form Page
4 for each).

Budget Justifications and Explanations: Describe the specific functions
of all key personnel, consultants, collaborators, and support staff. For all
years, explain and justify any unusual items such as major equipment or
alterations and renovations. For additional years of support requested, justify
any significant increases or decreases in any category over the first 12-month
budget period. Identify such changes with asterisks against the appropriate
amounts. If a recurring annual increase in personnel or other costs is
anticipated, give the percentage; however, current NIH practice limits
escalation to 3%. In addition, for COMPETING CONTINUATION applications, justify
any significant increases in any category over the current level of support.

PLEASE NOTE: Consortium budgets (if applicable) should be
presented as described in Composite Budget, including budget for the entire
proposed project period. Total direct and indirect costs of sub-awardee are to
be shown under Consortium/Contractual costs on the individual component budget
and a detailed sub-awardee budget is to be placed following the appropriate
Research Project or Core budget.

Biographical
Sketch (Biographical Sketch Format Page):

Follow the instructions on the Biographical Sketch Format
Page. This section must contain the biographical sketches of all individuals
listed as Senior/Key Personnel and Other Significant Contributors, following
the order listed on Form Page 2. Biographical sketches are required for
all key personnel participating in the Research Project components and Core
units. Begin with the P01 overall PD(s)/PI(s) and thereafter,
in alphabetical order, submit biographical sketches as described in the
Instructions for Form PHS-398. Do not exceed four pages for each person.

Resources
(Resources Format Page):

Complete the "Resources" page of PHS-398 for the
overall project. Briefly describe the features of the institutional environment
that are or would be relevant to the effective implementation of the proposed
program. As appropriate, describe available resources, such as clinical and laboratory
facilities, participating and affiliated units, patient populations,
geographical distribution of space and personnel, and consultative resources.

Research Plan

All instructions in the PHS398 Application Guide must be
followed, with the following additional instructions:

SECTION
II

Include a detailed Table of Contents with pagination
(numeric only) at the beginning of Section II.

Identify each Research Project component and each Core unit
by title. Assign each Research Project component a Roman numeral (I, II, III)
and assign each Core unit a capital letter (A, B, C) that reflects the order in
which they are presented.

For each Research Project component and Core unit, provide
the name of the responsible investigator, and biographical sketches for
personnel not identified previously.

Overview
of the Program Project (12 pages)

History
and Purpose of the Program

Discuss the overall P01 program's
objectives and general plans for the proposed grant period, including research
grant history with yearly funding level.

Administration,
Organization, and Operation

Include information on the support and
commitment of the parent institution for the program, the authority of the
PD/PI, the use of advisory committees, and space assignment. Describe organizational
framework and provide an organizational chart.

Research
Program

Discuss the proposed research program,
highlighting its central theme. List by title and investigator's name the
component Research Projects and Core units. Describe the relationship
between the projects and the Core units and their relationship to the central
theme.

Description
of Assurances and Collaborative Agreements

Provide an overview and rationale for
any collaborative and cooperative endeavors or subcontracts. Letters of agreement
for these arrangements are included in Item 6. Letters of Assurance/agreement
as described below.

Research
Project Descriptions (12 pages for each Research Strategy component)

Research Strategy (12 pages; Significance, Innovation, and
Approach): Start each section with the appropriate section
heading—Significance, Innovation, Approach. Cite published experimental details
in the Research Strategy section and provide the full reference in the
Bibliography and References Cited section. For new applications, include
information on Preliminary Studies. For renewal/revision applications, provide
a Progress Report within the 12 page research stategy limit. Indicate the
Research Project's use of Core unit services, including why needed and the
advantages and cost effectiveness of Core unit usage for the project.

Inclusion Enrollment Report (renewal or revision applications
only)

Bibliography and References Cited, Progress Report Publication
List

Protection of Human Subjects

Inclusion of Women and Minorities

Targeted/planned Enrollment Table

Inclusion of Children

Vertebrate Animals

Select Agent Research

Consortium/contractual arrangements

Letters of Support: Include pertinent letters of assurance
and collaboration for the Research Project.

For off-site projects, justification should be provided for the
project's location, and plans for interaction and cooperation with the other
components of the program should be addressed.

Resource Sharing Plan

Core
Unit Descriptions

Identify each proposed Core unit by a letter (A, B, C...) and a
title (e.g., Administrative Core, Molecular/Cellular Core, etc.).

A full description of each Core unit is to be provided following
the format presented in Form PHS-398.

Begin the presentation of each Core unit on a separate
page.

Cover
Page (1 page): Include the following on the Cover Page

Title of Core unit

Core Director (Principal Investigator), title, affiliation

Other investigators, titles, affiliations

Abstract
(1 page; use PHS-398 Form Page 2): Include an
Abstract that identifies and describes the purpose of the proposed Core unit.
Summarize the Core unit's overall objectives; highlight the
decision-making process for use of Core services and plans for
cost-effectiveness and quality control.

Introduction
(Resubmission or Revision Applications only; 1 page)

Core
unit Structure, Administration, and Services (6 pages)

Administrative Core Unit

Objective

Organizational chart (if appropriate)

Staffing (Professional and Support)

Resources: provide description of space and physical resources

Services provided (current and projected use): describe services
to other Core units and Research Projects

Additional Core Unit(s)

Objective

Staffing (Professional and Support)

Resources: provide description of space and physical resources

Administration

Justification: describe services provided with their bearing on
productivity and quality

List publications prepared during current grant period (or
the past five-year period) which report results of research supported by the
grant.

Letters
of Assurance/Agreement

Any arrangements for collaborative and cooperative endeavors
or subcontracts should be highlighted. Include letters of agreement from
consultants. For projects to be conducted off site, i.e., at an institution
other than the applicant institution, a PHS-398 face page or other
documentation, signed by the off-site institutional officials, must be
submitted with the application.

Resource Sharing Plan

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies; GWAS) as provided in the PHS398
Application Guide.

Appendix

Do not use the Appendix to
circumvent page limits. Follow all instructions for the Appendix (please note
all format requirements) as described in the PHS398 Application Guide.

Applicants requesting $500,000 or more in direct costs in
any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before
submitting the application and follow the Policy on the Acceptance for Review
of Unsolicited Applications that Request $500,000 or More in Direct Costs as
described in the PHS398 Application Guide.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115.

Section
V. Application Review Information

1. Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

For this particular
announcement, note the following:

For NICHD Program Project (P01) applications, peer review of
scientific and technical merit foruses on three areas: (1) review of the
individual Research Project components, (2) review of the individual Core
units; (3) review of the P01 program as an integrated collection of research
projects and cores oriented around a central theme as well as the overall merit
of the program.

Overall Impact - Overall Program Project

Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the Program Project to exert a sustained, powerful influence on the research field(s) involved, in consideration
of the following review criteria and additional review criteria (as applicable
for the Program Project proposed).

Scored Review Criteria - Overall Program Project

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a Program Project that by its nature is not innovative may be essential to advance a field.

Significance

Does the Program Project address an important problem
or a critical barrier to progress in the field? If the aims of the Program Project are achieved, how will scientific knowledge, technical capability, and/or
clinical practice be improved? How will successful completion of the aims
change the concepts, methods, technologies, treatments, services, or
preventative interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the Program Project? If Early Stage Investigators or
New Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD(s)/PI(s), do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions novel
to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the Program Project? Are potential problems, alternative strategies, and benchmarks for success presented?
If the project is in the early stages of development, will the strategy
establish feasibility and will particularly risky aspects be managed?

If the Program Project involves clinical research, are the plans for 1)
protection of human subjects from research risks, and 2) inclusion of
minorities and members of both sexes/genders, as well as the inclusion of
children, justified in terms of the scientific goals and research strategy
proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria - Overall Program Project

As applicable for the Program Project proposed, reviewers
will evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact/priority score, but will
not give separate scores for these items.

The Program as an integrated effort

The overall P01 program project application will be
evaluated as an integrated research effort focused on a central theme.
The relationship and contributions of each Research Project and Core to the
overall theme of the program project will be discussed and evaluated.
Reviewers will assign an impact/priority score based on assessment of the
scientific and technical merit of the overall program project. The assessment
will take into consideration all proposed Research Projects and Cores,
including any with poor ratings. Separate criterion scores for the
overall program will be assigned. The review will assess the level of
merit of the program project as an integrated effort, including the following
considerations:

The coordination, interrelationships, cohesiveness, and synergy
among the component Research Projects and Cores as they relate to the common
theme of the program project;

The advantages of conducting the proposed research as a program
project rather than through independent research projects;

The mechanisms proposed for regular communication and
coordination among investigators in the program;

The appropriatemess of administrative structures and day-to-day
management of the program.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed Program Project involves clinical research, the committee will evaluate the proposed plans for
inclusion of minorities and members of both genders, as well as the inclusion
of children. For additional information on review of the Inclusion section,
please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound research
including the use of analgesic, anesthetic, and tranquilizing drugs and/or
comfortable restraining devices; and 5) methods of euthanasia and reason for
selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the
application as now presented, taking into consideration the responses to
comments from the previous scientific review group and changes made to the Program
Project.

Renewals

For Renewals, the committee will consider the
progress made in the last funding period.

Revisions

For Revisions, the committee will consider the
appropriateness of the proposed expansion of the scope of the Program Project.
If the Revision application relates to a specific line of investigation
presented in the original application that was not for recommended approval by
the committee, then the committee will consider whether the responses to
comments from the previous scientific review group are adequate and whether
substantial changes are clearly evident.

Additional Review Considerations - Overall Program Project

As applicable for the Program Project proposed, reviewers
will consider each of the following items, but will not give scores for these
items, and should not consider them in providing an overall impact/priority
score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a component project that by its
nature is not innovative may be essential to advance a field.

Significance

Does the component project address an important
problem or a critical barrier to progress in the field? If the aims of the component
project are achieved, how will scientific knowledge, technical capability,
and/or clinical practice be improved? How will successful completion of the
aims change the concepts, methods, technologies, treatments, services, or
preventative interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the component project? If Early Stage Investigators
or New Investigators, or in the early stages of independent careers, do they
have appropriate experience and training? If established, have they
demonstrated an ongoing record of accomplishments that have advanced their
field(s)? If the project is collaborative or multi-PD(s)/PI(s), do the
investigators have complementary and integrated expertise; are their leadership
approach, governance and organizational structure appropriate for the
project?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the component
project? Are potential problems, alternative strategies, and benchmarks for
success presented? If the project is in the early stages of development, will
the strategy establish feasibility and will particularly risky aspects be
managed?

If the component project involves clinical research, are the plans for 1)
protection of human subjects from research risks, and 2) inclusion of
minorities and members of both sexes/genders, as well as the inclusion of children,
justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

As applicable for the component project proposed, reviewers
will evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact/priority score, but will
not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed component project involves clinical
research, the committee will evaluate the proposed plans for inclusion of
minorities and members of both genders, as well as the inclusion of children.
For additional information on review of the Inclusion section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary
care; 4) procedures for limiting discomfort, distress, pain and injury to that
which is unavoidable in the conduct of scientifically sound research including
the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable
restraining devices; and 5) methods of euthanasia and reason for selection if
not consistent with the AVMA Guidelines on Euthanasia. For additional
information on review of the Vertebrate Animals section, please refer
to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the
application as now presented, taking into consideration the responses to
comments from the previous scientific review group and changes made to the component
project.

Renewals

For Renewals, the committee will consider the
progress made in the last funding period.

Revisions

For Revisions, the committee will consider the
appropriateness of the proposed expansion of the scope of the component project.
If the Revision application relates to a specific line of investigation
presented in the original application that was not for recommended approval by
the committee, then the committee will consider whether the responses to
comments from the previous scientific review group are adequate and whether
substantial changes are clearly evident.

As applicable for the component project proposed, reviewers
will consider each of the following items, but will not give scores for these
items, and should not consider them in providing an overall impact/priority
score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

Review Criteria for Core Components

Reviewers will assign a score for each core unit component,
based on the assessment of each Core unit independently in terms of the
specified review criteria for Cores (see below). Cores will not receive scores
for the five standard criteria (significance, investigator(s), innovation,
approach, environment).

For
all Cores, the following review criteria will be used:

Are the qualifications, experience, and commitment of the core
director and other core personnel appropriate?

Will the quality of services provided enable center investigators
to achieve their research goals?

Is there cost effectiveness in the core; will there be quality
control measures taken for core procedures?

Is the proposed use of core services by the budgeted subprojects
appropriate?

For
the Administrative Core, the following review criteria will be used:

Does the core director have experience in research
administration?

Is there a decision-making process within the proposed center for
the evaluation of research productivity, for allocation of funds and for
management of the resources?

What is the overall strength of the plan for center evaluation,
including the use of any internal and external advisory groups?

What is the overall strength of the internal data sharing and
publication plan?

2. Review and Selection Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s), convened by the NICHD, in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall
impact/priority score.

Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and will
compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of
review by the National Advisory Child Health and Human Development (NACHHD) Council. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD(s)/PI(s) will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH
Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.